Dialysate Compartment Research Articles

Effects of novel manufacturing technology on blood and dialysate flow distribution in a new low flux "alpha Polysulfone" hemodialyzer.

The main target for low flux hemodialyzers is an efficient low molecular weight solutes clearance. Such efficiency is largely dependent on the optimization of diffusion between blood and dialysis solution. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. Thus optimized flow distribution both in the blood and dialysate compartment becomes quintessential for the maximal efficiency of the diffusion process within the hemodialyzer. The present paper describes the distribution of the blood and dialysate flows in a new low flux polysulfone hollow fiber hemodialyzer characterized by a specific undulation of the fibers and a new cutting technology of the fibers for an improved micro-flow condition in the blood compartment headers. Twelve Diacap alpha Polysulfone LO PS 15 (1.5 sqm) (B. Braun Medizintechnologie, Melsungen Germany) were employed for the study. Six were analyzed in vitro and six were studied in vivo. Blood flow distribution was studied in vitro by dye injection in the blood compartment during experimental extracorporeal circulation utilizing human blood with hematocrit adjusted at 33%. Sequential images were obtained with a helical scanner in a fixed longitudinal section of the dialyzer 1 cm thick. Average and regional blood flow velocities were measured utilizing the reconstructed imaging sequence. The method allowed the calculation of single fiber blood flow (SF Qb) and the mass transfer zone (MTR) definition in digitally subtracted images. The patterns 20-10 and 40-30 were utilized. The same technology was used to evaluate flow distribution in the dialysate compartment after dye injection in the Hansen's connector. Regional dialysate flow was calculated in central and peripheral sample areas of 1 cm2. Six in vivo hemodialysis treatments on patients with end stage renal disease were performed at three different blood flow rates (250-350 and 450 ml/min) in order to measure urea, creatinine and phosphate clearance. Macroscopic and densitometrical analysis revealed that flow distribution was homogeneous in the blood compartment while in the dialysate compartment a slight difference between the peripheral and central regions in terms of flow velocity was observed. This however was not generating channeling phenomena. Urea creatinine and phosphate clearances were remarkably high and so were the Kt/V observed in all sessions, especially in relation to the studied blood flows. In conclusion, a significant blood to dialysate flow match with optimized countercurrent flow condition was observed in the studied hollow fiber hemodialyzers. Such optimization might be due both to the improved dialyzer design at the level of the blood header and to the specific fiber undulation that prevents dialysate channeling.

Hollow fiber shape alters solute clearances in high flux hemodialyzers.

The mass transfer properties of hemodialyzers containing hollow fiber membranes are known to be influenced by membrane chemical composition, surface area, and pore size; however, the effects of hollow fiber shape (or configuration) and packing density within the dialyzer housing have not been well characterized. We determined, both in vitro and ex vivo (clinical), solute clearances and mass transfer-area coefficients (KoA) for high flux dialyzers containing polysulfone hollow fibers of identical chemical composition but different shapes. Hemoflow F80A (1.8 m2 of membrane surface area) dialyzers contained hollow fibers with a conventional shape, but Optiflux F180A (1.8 m2), F200A (2.0 m2), and F200NR (2.0 m2) dialyzers contained hollow fibers with a wavy shape. Clearances and KoA values determined in vitro for urea and creatinine increased with increasing dialysate flow rate and were higher for Optiflux F180A and F200A dialyzers than for Hemoflow F80A dialyzers. In vitro clearances for lysozyme and myoglobin were also higher for Optiflux F180A and F200A dialyzers than for Hemoflow F80A dialyzers, suggesting that a wavy hollow fiber shape increases mass transfer by increasing effective membrane surface area, conceivably by altering dialysate flow patterns. Urea clearances and KoA values determined ex vivo were higher for Optiflux F200NR dialyzers than for Hemoflow F80A dialyzers, confirming that the in vitro results are applicable to clinical hemodialysis. These increases in mass transfer efficiency for dialyzers containing hollow fibers with a wavy shape are consistent with improved mass transfer within the dialysate compartment as evidenced by the manufacturer-reported dialysate pressure-flow relationships. We conclude that the mass transfer characteristics of high flux dialyzers can be altered by the shape of the hollow fibers.

Faster phenytoin removal from serum by electrodialysis: a potential use in hemodialysis?

Protein binding of drug is responsible of ineffectiveness of conventional hemodialysis. The aim of the present study was to investigate the potential of electrodialysis, i.e. the transport of charged solutes through a membrane under the influence of an external electric potential, to increase the clearance of phenytoin, i.e. a model albumin-bound drug from human serum in vitro. Electrodialysis was performed through cellulose triacetate membrane mounted onto electrodialyser built in-house which separated: (a) saline solution, (b) 4% albumin saline solution or (c) human serum and dialysate compartments. The electric current density between both electrodes placed into donor (cathode) and dialysate (anode) compartments was settled to 0.79 mA/cm 2 for 3 h at 37 °C. Recovery of phenytoin in dialysate from either (a) saline solution or (b) 4% albumin saline solution was significantly higher than that obtained by classical dialysis ((a): 42% versus 24%; (b): 30% versus 6%). In human serum, the effectiveness of electrodialysis was appreciated by the unbound phenytoin clearance, which was about twice higher than in dialysis (0.22 ml/h versus 0.12 ml/h). However, the removed fraction of 10% in the human serum could just reflect the usual unbound phenytoin. Consequently, the impact of electrodialysis on the protein binding was not affirmed, but the ability of this technique to eliminate shortly free drug was clearly demonstrated. Electrodialysis would be a promising improvement of hemodialysis for the elimination of ionized drugs from human blood.

Hemodialyzer: From macro-design to membrane nanostructure; the case of the FX-class of hemodialyzers

Very few innovations have characterized the different components of the hemodialyzers in the past 20 years. Most improvements have concerned membrane biocompatibility. In this article, we focus our attention on the most recent advances in hemodialyzer components from the macro design of the unit to the nanostructure of the membrane. For this purpose, we took as an example the FX class of hemodialyzers (FMC, Bad Homburg, Germany). The studied devices were chosen as an example representing some of the most recent hemodialyzers and are well suited to describe technical innovations occurring in the field of dialyzer technology. In vitro and in vivo studies were performed to characterize hemodynamic parameters of three models (1.4-1, 8, and 2.2 m2) and to determine membrane permeability, sieving coefficients, and solute clearances. The units were characterized by a relatively high resistance of the blood and dialysate compartments, leading to an increased internal filtration if compared with similar hemodialyzers of other series. Nevertheless, the flow distribution in both compartments was homogeneous and well balanced. This effect was obtained by the improved blood and dialysate ports design, the increased packing density of the fibers and a reduction of the inner diameter of the fibers from 200 to 180 microm. At the same time, the sieving coefficients for middle-large solutes such as beta2 microglobulin and insulin were higher than those observed in standard high flux dialysers. The same effect was noted for the clearance values of these solutes. This was observed in the absence of significant albumin leakage. These results were obtained thanks to a new nano-controlled spinning technology applied to the fiber. The innermost layer of the membrane is in fact characterized by a homogeneous porosity, with increased number of pores of large dimension but a sharp cutoff of the membrane excluding albumin losses. In conclusion, new technologies and new diagnostic tools today allow for improvement in hemodialyzer design from its macro-components to its nano-structure. The application of nanotechnology to hemodialysis will probably contribute to further developments in hemodialyzer manufacturing.

Extracorporeal liver support by recirculating albumin dialysis: analysing the effect of the first clinically used generation of the MARSystem.

Albumin dialysis with the MARSystem is used in many hospitals to support excretory hepatic function in acute or acute on chronic liver failure. Potential pathogenic albumin bound substances accumulated in excretory liver insufficiency can be removed from patients blood by dialysis against albumin solution. A specific membrane enables the selective transport of albumin bound metabolites to the albumin containing dialysate compartment, where the loaded transport albumin is cleared and regenerated at the same time by adsorption columns and a second dialyser. Between 1993 and 1995 different membranes, set-ups and components in albumin dialysis were tested and led finally to the recirculating MARSystem with a modified polysulphone based membrane (P3/5S Gambro, Hechingen) and two adsorption columns (N350 and BR 350, ASAHI Medical Ltd.), which showed the best performance at this time. This first generation of MARSystems was used clinically between 1995 and 1998 with only minor changes in 15 patients with acute (n = 1) or acute deterioration of chronic liver disease in our department until the improved next generation of MARSystems has been available (MARS set and monitor, Teraklin AG, Rostock, Germany). Changes in blood tests pre/post during 95 single MARS treatments and in clinical status over treatment period were evaluated retrospectively. A significant decrease of albumin bound substances (average reduction during single MARS treatments: bilirubin -18%, bile acids -43.7%) as well as of water soluble metabolites (creatinine -32%, urea -31%) was observed. During extracorporeal therapy also a significant drop in platelets (- 15.4%) and a prolongation of activated prothrombin time (- 21%) was documented, whereas haemoglobin, WBC, electrolytes as well as transaminases and albumin were not affected significantly. Albumin dialysis with the first generation of MARS enables the removal of albumin bound and water soluble toxins. Unwanted side-effects and changes in laboratory tests are comparable to conventional haemodialysis (drop of platelets and prolongation of coagulation tests). The elimination of albumin bound and water soluble substances was accompanied by an improvement of clinical status.

Development of a novel electro-dialysis based technique for lead removal from silty clay polluted soil

In this study, a novel electro-dialysis based technique has been developed and used to treat a silty clay soil polluted by lead. The effect of chemical reagents, i.e. tap water at pH 4 (reagent 1) and sodium acetate at pH 5 (reagent 2), on enhancing electro-dialysis extraction of lead from the tested soil was examined. Specimens were prepared by mixing soil with 1000 ppm of lead and were compacted in the dialysate at predetermined dry density and moisture content. Then, specimens were subjected to a predetermined level of current. In the dialysate compartment, anions and cations were removed by charge transport in opposite directions to the anodic and cathodic cells. Meanwhile, in the anodic and cathodic cells, ion concentrations were increased. Thus, concentrated electrolyte streams were produced in alternating cells and cleaned soils were obtained in the dialysate. Both soil pH and lead concentrations were uniformly distributed within the compacted soil specimen during testing. Total lead removal of 80 and 92% was obtained for reagents 1 and 2, respectively. The high removal efficiency was attributed to the separation of electrode reactions from the soil and inclusion of ion selective membranes (ISM), which restrict the movement of counter charged species.

DO INDUCED SECONDARY FLOWS AUGMENT THE CLEARANCE OF PROTEIN-BOUND SUBSTANCES DURING ALBUMIN HEMODIAFIL-TRATION?

Objective: Removal of protein-bound toxins such as bilirubin by albumin hemodiafiltration (HDF) has been applied in patients with hepatic failure. As toxins must he transferred from perfusate to dialysate albumin binding sites, the efficiency of HDF may be limited by the laminar flow in the filter compartments where only a thin layer of fluid contacts the fiber surface. We hypothesized that disruption of laminar flow through filter agitation would enhance bilirubin transfer during HDF. Methods: An in vitro continuous HDF circuit was used with fixed volume perfusate and dialysate compartments. Unconjugated bilirubin was added to sheep plasma (10 mg/dl) and perfused through an albumin-impregnated polyalkyl sulfone hemofilter against a recirculating albumin-rich dialysate (10 g/dl) with matched flow rates. One group of filters (n = 3) was vigorously agitated during HDF along its long axis at approximately 8 Hz. A second group (n = 3) remained stationary. Plasma bilirubin levels were maintained between 8 and 12 mg/dl by continuous infusion of bilirubin. Dialysate bilirubin concentrations were measured over 3 hours. Bilirubin transfer rates were compared using repeated-measures ANOVA. Results: At 3 hours, 19% more bilirubin was transferred by the agitated filter than by the stationary filter (22.5±3.8 vs. 18.9±2.3 mg, p = NS). The transfer rate was highest for both groups in the first 30 minutes, but was 70% greater in the agitated filter (0.233±0.064 vs. 0.137±0.024 mg/min, p=0.068). However, this rate difference was not maintained beyond 90 minutes. Conclusions: Bilirubin transfer may be enhanced by the introduction of secondary flows, especially in the first 90 minutes of HDF. Mixing at the fluid-fiber interface may be an important determinant of hemofilter performance. Further studies to elucidate the factors responsible may influence future hemofilter design and ultimately the efficiency of extra-corporeal hepatic support.

Blood and Dialysate Flow Distributions in Hollow-Fiber Hemodialyzers Analyzed by Computerized Helical Scanning Technique

ABSTRACT. The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion between blood and dialysis solution. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. This article describes the distribution of the blood and dialysate flows in hollow-fiber hemodialyzers analyzed with a computerized scanning technique. Blood flow distribution was studied in vitro by dye injection in the blood compartment during experimental extracorporeal circulation using human blood with hematocrit (Hct) adjusted at 25 and 40%. Sequential images were obtained with a helical scanner in a 1-cm-thick fixed longitudinal section of the dialyzer. Average and regional blood flow velocity and wall shear rates were measured by using the reconstructed imaging sequence. The method allowed the calculation of single-fiber blood flow and single-fiber wall shear rate (SF wSh) in different regions of the hemodialyzer. In 38 patients on chronic hemodialysis, creatinine and phosphate clearance displayed a significantly negative correlation with Hct (P < 0.05), but this correlation was not found for urea, although a trend toward reduction could be observed. The suggested explanation of this phenomenon is the significant reduction in effective plasma water flow across the hemodialyzer in presence of a progressive rise in Hct. The second explanation for this phenomenon may be found in the nonhomogeneous distribution of blood flow within the fibers observed at the sequential imaging. This, in fact, could also explain the negative trend observed for urea. At higher Hct levels, single-fiber blood flow velocity and SF wSh were significantly lower in the fibers situated at the periphery of the bundle. At the same time, SF wSh tended to decrease in peripheral fibers, showing a value near half of that observed in the central fibers of the bundle (165 versus 301 s−1). A similar technique was used to study the flow distribution in the dialysate compartment in three different types of hemodialyzers with characteristic dialysate compartment design: (A) standard configuration; (B) space yarns (spacing filaments preventing contact between fibers); and (C) Moiré structure (wave-shaped fibers to prevent contact between adjacent fibers). Clinical sessions of hemodialysis were also carried out to measure blood- and dialysate-side urea clearances in the different hemodialyzers. Macroscopic and densitometric analysis revealed that flow distribution was most homogeneous in the dialyzer with Moiré structure (type C) and least homogeneous in the standard dialyzer (type A). Space yarns (type B) gave an intermediate dialysate flow distribution. Urea clearance (P < 0.001) increased significantly with types B and C, compared with the standard dialyzer. Type C had the highest clearances, although they were not significantly greater than type B. In conclusion, a significant blood-to-dialysate flow mismatch may occur in hollow-fiber hemodialyzers due to either uneven blood flow distribution or a dialysate channeling phenomenon external to the fiber bundle. Improvement in dialyzer design may overcome these problems, at least in part.

Pyrogen retention by highly permeable synthetic membranes during in vitro dialysis.

Pyrogen permeability of the new highly permeable synthetic membrane polyethersulfone (DIAPES) was compared to polysulfone in vitro dialysis experiments with heparinized human donor blood in the blood compartment. After sterile dialysis for 5 min, dialysate was contaminated with a culture filtrate of Pseudomonas aeruginosa using high and moderate challenge doses (Limulus assay reactivity 20,000 EU/ml and 50 EU/ml, respectively). Whole blood samples were separated from the blood compartment during the sterile (5 min) and contaminated (60 min) phases of dialysis and incubated for 6 h at 37 degrees C. Blood samples were lysed, and interleukin-1beta and tumor necrosis factor alpha were measured by specific ELISAs. Moderate dialysate contamination (50 EU/ml) did not induce detectable cytokine production in whole blood. High challenge dose (20,000 EU/ml) induced whole blood interleukin-1beta and tumor necrosis factor alpha production in the blood compartment, which was higher with DIAPES than with polysulfone after 30 min. After 60 min, membrane-dependent differences were no longer detectable. Pyrogen concentrations in the dialysate decreased with time indicating adsorption of cytokine-inducing substances to the dialyzer membrane. Pyrogens adsorbed to dialyzer membranes were resuspended during recirculation of sterile phosphate-buffered saline in the dialysate compartment and retained cytokine-inducing activity as seen from whole blood incubation experiments. DIAPES and polysulfone adsorbed pyrogens in the presence of whole blood. Pyrogen adsorption to the membrane polymer and/or to the protein coat on the membrane prevented the passage of pyrogens in the presence of moderately contaminated dialysate. High grade dialysate contamination caused breakthrough of pyrogens into the blood with DIAPES and polysulfone. In order to reduce the risk of a dialysis-dependent inflammatory response, dialysate of high bacteriological quality (ultrapure dialysate) should be mandatory.

Impact of contaminated dialysate on long-term haemodialysis-related complications: is it really that important?

Recently, in haemodialysis (HD) concern has been raised about the long-term consequences of non-sterile dialysate and the concomitant use of dialysers with large pore size, usually high-flux devices w1,2x. According to current opinion, monocytes are activated by the repeated transfer of bacteria-derived substances from the dialysate compartment to the circulation of the patient, resulting in the secretion of a variety of proinflammatory cytokines, such as interleukin-1b (IL-1b), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFa). Due to the recurrent character of the stimulus, a chronic inflammatory state is induced, leading to a number of long-term HD-related complications, such as infections, malnutrition, dialysis-related amyloidosis (DRA), accelerated atherosclerosis and increased mortality w3x. However, the cause and nature of HD-induced monocyte activation is a controversial issue. Various provoking factors have been recognized, including complement activation w4x, coagulation w5x, mechanical stress and shear forces w6x and direct contact between blood cells and the membrane of the dialyser w7x. In addition, dialysate factors, such as the presence of acetate w8x and the backtransfer of contaminated dialysate may induce cell activation as well. In the following section we will discuss the arguments supporting backtransport of endotoxins (ETX), which are mainly indirect. Thereafter, we will review the available evidence with reference to backtransport of contaminated dialysate in clinical practice, as measured by antibodies against ETX, the appearance of limulus amoebocyte lysate (LAL) activity in the blood during HD, and recent clinical intraand peri-dialytical data relating to this topic. Finally, we shall review a number of relevant clinical follow-up studies with respect to the occurrence of long-term complications during HD with different types of dialysers.

Factors affecting hemodialysis and peritoneal dialysis efficiency.

Hemodialysis and peritoneal dialysis are two blood purification techniques that use similar operating systems. The hemodialysis system is based on three components (blood, membrane, and dialysate). The peritoneal dialysis system is based on the same components that can, however, be less manipulated and adjusted. In hemodialysis the blood flow is the main determinant of small solute removal thanks to a prevalently diffusive mechanism. Convection is also used to transport larger solutes across the membrane, but this mechanism relies on the high permeability coefficient of the membrane and high transmembrane pressure leading to high ultrafiltration rates. The membrane can therefore influence the performance of the techniques as far as solute removal and ultrafiltration are concerned. Finally, diffusion is facilitated by an improved distribution of dialysate flow in the dialysate compartment. This can be achieved with a special dialysate pathway configuration based on space yarns or micronodulation of the fibers. In peritoneal dialysis, blood flow and membrane characteristics can be less manipulated or almost not at all. The only variables are dialysate volume, flow, dwell time, and composition. Thanks to modification in these aspects of the dialysate, peritoneal dialysis techniques with different clearances and ultrafiltration rates can be accomplished.

Dialysate Flow Distribution in Hollow Fiber Hemodialyzers with Different Dialysate Pathway Configurations

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, since this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different dialysate compartment designs on dialysate flow distribution and urea clearances. Eighteen hollow fiber 1.3 m2 hemodialyzers were studied, 6 each of 3 designs: Type A--standard fiber bundle (PAN 65DX Asahi Medical, Tokyo, Japan); Type B--spacing filaments external to the fibers (PAN 65SF Asahi Medical, Tokyo, Japan); Type C--fibers waved to give Moiré structure (FB130 Nissho-Nipro, Osaka, Japan). 3 dialyzers of each type were studied following dye injection into the dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer were undertaken, using a new generation helical CT scanner (X-Press/HS1 Toshiba Corporation, Tokyo, Japan). In vivo studies: 3 dialyzers of each type were studied, in randomized sequence, in 3 different patients under standardized dialysis conditions. Blood- and dialysate-side urea clearances were measured at 30 and 150 minutes of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with Moiré structure (Type C) and least homogeneous in the standard dialyzer (Type A). Space yarns (Type B) gave an intermediate dialysate flow distribution. Significantly increased urea clearances (p<0.001) were seen with Types B and C, compared to the standard dialyzer. Type C (Moiré) had the highest clearances although these were not significantly greater than Type B (space yarns). In conclusion, more homogeneous dialysate flow distribution and improved small solute clearances can be achieved by use of spacing yarns or waved (Moiré structure) patterns of fiber packing in the dialyzer. These effects are achieved probably as a result of reduced dialysate channeling resulting in a lower degree of mismatch between blood and dialysate flows. The new radiological technique using the helical CT scanner allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.

Effects of a reduced inner diameter of hollow fibers in hemodialyzers

The clearance of middle molecules in high-flux hemodialyzers is due to the higher contribution of convection in the overall solute transport. Although net filtration can be maintained low by the machine control, internal filtration in the proximal part of the dialyzer remains high. The final fluid balance is achieved by significant amounts of backfiltration in the distal part of the dialyzer. To increase further middle molecule clearance (MMK), hemodiafiltration has been used. This technique, however, requires complex machines and large amounts of substitution fluid. We present a novel solution to increase the convective transport of middle molecules in high flux dialyzers without the need for substitution fluids. In particular, high-flux dialyzers with a reduced hollow fiber diameter are compared with standard dialyzers in terms of internal filtration and solute clearances. Hemodialyzers with 175 micro inner diameter polysulfone fibers were compared with standard 200 micro polysulfone hollow fiber dialyzers. The study was carried out in vitro using a previously published method to measure internal filtration and backfiltration rates. The method is based on the detection by a gamma camera of segmental variations in concentration along the length of the dialyzer of a nondiffusable Tc99-labeled marker molecule injected in the blood in vitro circuit. At the same time, pressures were detected in the blood and dialysate compartment. The system was operated at zero net filtration maintaining volumetrically constant both dialysate and blood circuits. In vivo clearances were also measured for solutes with different molecular weight. The pressure drop in the blood compartment at 300 mL/min of blood flow passed from 112 to 159 mm Hg. At the same blood flow, the internal filtration-backfiltration rates increased from 23. 1 to 48.2 mL/min. This resulted in a significant increase of in vivo in clearances of vitamin B12 and inulin of more than 30%. Urea, creatinine, and phosphate clearance did not display any change. A reduction of the inner diameter of the hollow fibers in high-flux dialyzers may result in a significant increase of the blood compartment resistance. In turn, this results in increased rates of internal filtration and backfiltration. The practical effect in clinical dialysis is demonstrated on middle molecules. While, in fact, the clearances for small solutes such as urea and creatinine are not affected, the clearances of larger solutes such as vitamin B12 or inulin increase significantly (P < 0.01).

Bradykinin and nitric oxide generation by dialysis membranes can be blunted by alkaline rinsing solutions

Bradykinin (BK) generation following the first contact of blood with the dialysis materials is thought to enhance hypersensitivity reactions (HSRs). Some of the effects of BK are mediated by nitric oxide (NO). We have recently reported that the pH of diluted blood modulates the kinin system. The present study was aimed to investigate the role of the pH of culture media and filter-washing solutions and BK and NO generation, either in vitro and ex vivo. BK was measured by a specific enzyme-linked immunosorbent assay (ELISA), and NO synthase (NOS) activity by 3H-citrulline production after incubation with 3H-arginine and nitrites by using the Griess reagent. In in vitro experiments, NOS activity was detected in endothelial cells (ECs) cultured with graded BK concentrations at various pH values. Blood from 30 patients in regular dialysis was ex vivo circulated in one single passage through minifilters prerinsed with pH 7 or pH 8 phosphate buffer (PB) solutions. The out-flowing blood was tested for BK and nitrite content and was incubated with cultured ECs to evaluate its capacity to modulate NOS activity. BK induced in vitro a dose-dependent increase in NOS activity of ECs, which was mediated by tyrosine kinase phosphorylation. NO generation was enhanced at pH 7.2, which remained unchanged at pH 7.6. In ex vivo experiments, blood out-flowing after one passage on filters washed with pH 7 PB solutions had increased BK levels (P < 0.0001), increased nitrites (P < 0.05), and enhanced EC NOS activity (P < 0. 05) in comparison to data found when filters were washed with pH 8 PB. Only when the filters were rinsed with a solution at pH 7 did PAN DX and AN69 membranes show a distinct BK generation capability, and cuprophane a peculiar capability to enhance NOS. Such effects were prevented when dialyzers were prerinsed with pH 8 PB. Multiple regression analysis showed that the pH of the uremic blood was the driving factor for BK and NOS activation (r = 0.54, P < 0.02). BK and NO generation are modulated by environmental pH. Rinsing the blood and dialysate compartments of filters with an alkaline solution prior to use may mitigate the activation of mediators likely to be involved in some HSRs.

Pyrogen Retention by the Asahi APS-650 Polysulfone Dialyzer during In Vitro Dialysis with Whole Human Donor Blood

The purpose of this study was to test the pyrogen permeability of the new Asahi polysulfone APS 650 (APS) dialyzer membrane with a high permeability for middle molecules (up to 40 kDa) in comparison with the high-flux Fresenius polysulfone F60S (F60S) membrane. Dialyzers were tested in parallel in vitro dialysis experiments with whole human donor blood in the blood compartment and contaminated bicarbonate dialysate in the dialysate compartment. Dialysate was contaminated by a filtrate (0.45 microm) of a Pseudomonas aeruginosa culture in bicarbonate dialysate. The production of interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in whole blood samples taken from the in vitro dialysis system was used to detect the passage of cytokine inducing bacterial substances derived from P. aeruginosa across the two highflux polysulfone membranes. Compared with a sterile control period at the beginning of each experiment (n = 5), the TNFalpha inducing activity in the dialysate increased from (mean +/- SEM) 42 +/- 12 pg/ml to 1,288 +/- 356 pg/ml with F60S dialyzers and from 37 +/- 10 pg/ml to 928 +/- 249 pg/ml with APS dialyzers 30 minutes after the dialysate was contaminated. The IL-1beta inducing activity in the dialysate increased similarly. In the presence of this significant contamination in the dialysate, whole blood circulating in the blood compartments for 60 minutes was not stimulated to produce increased amounts of TNFalpha or IL-1beta with neither of the two tested membranes. We conclude that F60S and APS membranes are equal in their ability to prevent the passage of cytokine inducing bacterial substances from highly contaminated dialysate into the patients' blood during hemodialysis.

Analysis of the effects of increasing delivered dialysis treatment to malnourished peritoneal dialysis patients

Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of QD, QB, and ultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data. Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included QB of 300 and 400 mL/min and QD of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates. The ultrafiltration rate and clearance were significantly correlated (R > 0.9, P < 0.001) and fitted a linear model (P < 0.001) in all of the experimental conditions. The following formula fitted the experimental points with an error <2% for both postdilutional and predilutional online diafiltration in vitro, respectively. K = K0 + [(QB - K0)/(QB)] x ultrafiltration rateK = K0 + [((QD x QB)/(QB + QD) - K0)/QD] x ultrafiltration rate where K is the clearance; K0 is the clearance with nil ultrafiltration rate; QD is the total dialysate produced (in commercial HDF, QD = QDi + Qinf). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. QB is the "blood" line flow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a QB taking into account the cellular and water compartments. In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.

Influence of convection on small molecule clearances in online hemodiafiltration Technical Note

Influence of convection on small molecule clearances in online hemodiafiltration. Background Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of Q D , Q B , andultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data. Methods Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included Q B of 300 and 400 mL/min and Q D of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates. Results The ultrafiltration rate and clearance were significantly correlated ( R > 0.9, P P where K is the clearance; K 0 is the clearance with nil ultrafiltration rate; Q D is the total dialysate produced (in commercial HDF, Q D = Q Di + Q inf ). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. Q B is the “blood” lineflow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a Q B taking into account the cellu-lar and water compartments. Discussion In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.

Haemodialysis filters: what's new?

Haemodialysis techniques rely on efficient haemodialyzers that are utilized as solute and water exchangers. The haemodialyzer design has not changed significantly for many years. Only recently optimization of the blood compartment design, of the membrane structure and of the dialysate compartment geometry have been sought. This paper briefly reviews the most recent advances in the design and construction of haemodialyzers and points out the clinical impact of such innovations.

In Vitro and in Vivo Evaluation of a New Polysulfone Membrane for Hemodialysis. Reference Methodology and Clinical Results: (Part 1: In Vitro Study)

Different high flux membranes have been recently developed. The present study is aimed at describing the technical features and the clinical performances of a new high flux polysulfone membrane (T-sulfone, Toray, Japan). The study has been carried out on two different dialyzers (surface area = 1.3 and 1.8 m2). The filters have been tested in vivo during hemodialysis and hemodiafiltration. The in vivo study was carried out on 12 ESRD patients on regular hemodialysis treatment. The protocol was reviewed and approved by the local ethical committee. The in vivo clearances (K) at 300 ml/min of blood flow are reported in the following Table: [Table in text]. Beta-2-m reduction ratio exceeded 50% in all sessions. Beta-2-m mass balance executed by collection of spent dialysate and elution from the used filters evidenced that removal is obtained mostly by filtration while absorption is negligible. Excellent tolerance and hemocompatibility was observed in all the studied sessions.

Enhancement of convective transport by internal filtration in a modified experimental hemodialyzer: Technical note

Hemodialysis using high flux membranes today is a commonly used therapy. The primary advantage is the larger spectrum of molecules removed with these membranes, and the mechanism of removal is in part due to a phenomenon of filtration and backfiltration along the length of the hollow fibers. We hypothesized that increasing the filtration and backfiltration fluxes by modifying the structure of the dialyzer could enhance the convective transport of various solutes. A modified high flux dialyzer was compared to the standard model in terms of pressure profiles, filtration-backfiltration rates and solute clearances. The modification consisted on the placement of a O-ring around the fiber bundle to create a resistance for the flow of the dialysis solution external to the fibers. The study on filtration fluxes was carried out using a scintigraphic method previously described, and solute clearances were studied during ultrafiltration-controlled hemodialysis sessions. Utilizing a net filtration condition proximal to zero, the rates of proximal filtration and distal backfiltration in the experimental dialyzer were significantly enhanced in comparison with the standard dialyzer. The pressure drop in the dialysate compartment could be increased significantly, thus permitting an increase in the positive transmembrane pressure in the first half of the dialyzer and a parallel increase in the negative transmembrane pressure in the second half of the dialyzer. This resulted in a significant enhancement of the convective transport of middle-large solutes as demonstrated by the increase in vitamin B12 and inulin clearances. This approach suggests that changes in design of the dialyzer may affect its performance. The use of internal filtration is suggested to improve convection and dialyzer efficiency for larger solutes without the requirement for high volumes of replacement fluid, as is the case for current hemodiafiltration techniques.